Mouse F1 spleen cells develop cytotoxic activity in vitro against parental cells. The antigenic differences detected appear to be controlled by a structural gene (Hh-1) mapping in or near the D region of the H-2 complex. Although a number of positive correlations have been demonstrated between murine hemopoietic graft rejection in vivo and F1 anti-parent cytotoxicity in vitro, certain differences have been found between these two F1 anti-parent reactions. These include the observations that marrow graft rejection does not require priming and is not dependent upon thymus-dependent cells, whereas the development of cytotoxic cells requires sensitization and is effected by T-lymphocytes. The same mechanism is also responsible for the rejection of homopoietic allografts. Injection of F1 mice with parental spleen cells (which have graft vs. host potential) results in the specific abrogation of F1 anti-parent reactions in vitro and in vivo, whereas injection of parental bone marrow is associated with some degree of priming for F1 anti-parent cytotoxicity.